Rituximab in multiple sclerosis at general hospital level

Abstract

| 491 wileyonlinelibrary.com/journal/ane | INTRODUC TI ONSeveral new disease-modifying therapies (DMTs) have emerged during the last decades for people with multiple sclerosis (MS), which brings both opportunities and challenges to daily praxis. There are multiple issues other than drug efficacy that must be addressed before deciding on treatment modality. Besides disease-related inflammatory aggressiveness and subjects' susceptibility to drug-specific adverse events, subjects' preferences, and cost-benefit aspects also have to be taken into consideration. As a consequence, a gap is developing between the national guidelines authorized by the Swedish Medical Products Agency 1 and real-life treatment selection.Sweden stands out with its high use of off-label rituximab (RTX), representing approximately 40% of all ongoing DMTs in MS care. 2 Furthermore, a Swedish study that included subjects with MS from three tertiary academic hospitals showed that as many as 53.3% of all subjects were given RTX as the primary DMT for MS. 3 The published data extracted from the Swedish MS registry show increased Objectives: The use of rituximab (RTX) in multiple sclerosis (MS) is a rapidly increasing choice of disease-modifying therapy. Efficacy outside specialized university hospital-based care is not yet systematically investigated. Our aim was to evaluate off-label RTX treatment for MS at a general hospital in Sweden. Materials and Methods: Subjects with definite MS with at least one rituximab infusion were eligible for inclusion in this retrospective, observational study. Effect was evaluated by monitoring clinical disability, annual relapse rate, new lesions on MRI, and safety by the incidence and severity of adverse events. Results: Among the 83 included subjects, 15 had clinical worsening of disease during the median 23.5 (1-76) months of follow-up after RTX initiation: 7/66 with relapsing-remitting multiple sclerosis (RRMS) and 8/17 with progressive subtypes (PMS).Cumulative survival without worsening was 86% in RRMS and 30% in PMS. The annual relapse rate before RTX vs follow-up dropped from 0.38 to 0.05 (P < .00001).Subjects with new enhancing lesions on MRI during the first year before RTX initiation vs the year after dropped from 0.94 to 0.024 (P < .00001) and was only seen in RRMS (1.05-0.31, P = .00003). Adverse events were mainly mild. Thirty-six out of 53 non-infusion-related adverse events were infections, of which four were serious, including a case of pneumonia with concomitant late-onset neutropenia. Conclusions:Rituximab was as effective and safe when given at a general hospital outpatient clinic compared with results from previous university hospital-based studies. Vigilance is required concerning severe adverse events. K E Y W O R D Smultiple sclerosis, rituximab, safety management

Safety and efficacy of rituximab as first- and second line treatment in multiple sclerosis – A cohort study

“…Late onset neutropenia is a well-known side effect of rituximab treatment 18 but has only been documented in few MS-patients treated with rituximab in retrospective studies. 19,20 Our results indicate that neutropenia may be underreported if not monitored.…”

Rituximab for the treatment of multiple sclerosis: a review

“…An increasing body of evidence supports the high efficacy and the low drug discontinuation rate of B-cell-depleting anti-CD20-antibody RTX for the treatment of MS. Longterm observation of RTX therapy in RA and in NMOSD suggests that RTX is highly effective, safe and well tolerated [38,41,70,81,85]. Two large randomized clinical trials and results from large real-world studies have confirmed its safety and efficacy in both RRMS and PMS [31,37].…”

“…Overall, there were similar incidences of infections in the placebo (71.4%) and RTX group (69.7%) in the first phase II study in MS; however, an increased incidence of urinary tract infections and sinusitis was found in RTX arm compared to placebo [31]. In a recent retrospective observational study of 84 relapsing MS treated with RTX, 36 infections were reported (among 53 non-infusion-related adverse events), of which four were serious, including a case of pneumonia with concomitant late-onset neutropenia [85].…”

Rituximab and risk of COVID-19 infection and its severity in patients with MS and NMOSD

“…Particularly, Rituximab (RTX), a chimeric monoclonal antibody directed at CD20 positive B lymphocytes is considered a selective immunosuppressant used in different in clinical practice (500-1000 mg, every 3-6 months, or on demand at B cells detection of ≥2% of B cells) [7][8][9][10]17]. Recent real-world experiences have shown that patients with either NMO or MS disease benefit efficiently from RTX with favorable safety and cost-effectiveness profile [17][18][19][20]. However, It has been suggested that the risk of serious infection for patients with MS or NMOSD varies depending on the DMTs being used.…”